The Effets Of Hepatic Deletion Of FKBP38 Gene On Liver Functions

Objective:To investigate the effects of hepatic deletion of FKBP38 on liver functions by studying the mouse model of FKBP3 8 conditional knockout in liver.Methods:1.Genetically engineered mouse whose FKBP38 gene was flanked with loxP was constructed by embryo microinjection.The FKBP38 gene was deleted by breeding mice harboring two loxP sites in FKBP38(FKBP38fl/fl)with the mice bearing the expression of Cre recombinase mice driven by an album promoter.Afterwards,the genotype of FKBP38 conditional knockout mice was analyzed.2.Hepatic apoptosis and liver functions were analyzed by ELISA,TNEL staining,and Western Blot assays.3.Mouse liver was analysed in histopathology analysis.Results:1.The expression levels of hepatic FKBP38 mRNA and protein showed significant difference between FKBP38 conditional knockout mice(FKBP38-/-)and wild type(P<0.001).2.The phosphorylation of hepatic p70 S6K of FKBP38 was moderately elevated,and the phosphorylation of hepatic 4EBP1 moderately decreased,in the conditional knockout mice(FKBP38-/-)compared with those of the wild type.3.Body weight of FKBP38 conditional knockout mice(FKBP38-/-)were essentially no different from which of the wild type mice,while blood fasting glucose concentrations of FKBP3 8 conditional knockout mice(FKBP3 8-/-)were significantly decreased from those of the wild type mice.4.No significant differences in the expression of hepatic BCL-2 and hepatocyte apoptosis were observed between the FKBP38-/-and wild type mice.5.Aspartate transaminase(AST)and Alanine aminotransferase(ALT)levels is not different between FKBP38 conditional knockout mice(FKBP38-/-)and the wild types.6.No significant hyperplastic lesions showed in both FKBP38 conditional knockout mice(FKBP38-/-)and wild type ones.7.The number of hepatocytes was significantly reduced in the FKBP38 conditional knockout mice.Conclusions:1.The genetic mouse model of the gene FKBP38(FK506 binding protein 38)conditional knock out in liver was constructed successfully.2.Blood fasting glucose concentrations of FKBP38 conditional knockout mice(FKBP38-/-)were significantly decreased.3.Hepatic FKBP38 deletion has a moderate stimulatory effect on mTOR activity.4.Apoptosis and apoptosis associated factor,bcl-2,is not significantly affected when FKBP38 is deleted.5.The number of hepatocytes was significantly reduced in the FKBP38 conditional knockout mice.